Gut health and immune health delivered via probiotics

Probiotics today are consumed primarily through fermented dairy products such as yoghurt and kefir, and also in supplement formulations. A growing body of evidence is confirming the positive effects of probiotics in humans, primarily related to two major areas: gastrointestinal and immune health. Amy Fitzpatrick tells all.

Although a variety of bacteria have been commonly consumed through our food supply for millennia, it wasn't until the turn of the century that ingested bacteria were proposed to have a positive influence on the normal microbial flora of the intestinal tract, which in turn would affect the health of humans.

Researchers have now estimated that microflora in the adult human body consist of an enormous biomass of >100,000 billion bacteria of >400 different species, which generate metabolic activity and play an important physiologic role in humans.1

Lactobacillus and bifidobacteria are the two genera of greatest research and use regarding human health. These two groups of 'friendly' bacteria live symbiotically in our bodies in a beneficial relationship that enhances our health in a wide variety of ways. Lactobacillus organisms reside mainly in the small intestine, bifidobacteria in the large. The lactobacillus genus contains dozens of species, including such organisms as L acidophilus, L plantarum, L casei, L rhamnosus, L paracasei and L reuteri.

Some of the most important members of the bifidobacteria genus include B longum, B bifidum, B breve, B lactis and B infantis. Scientists are now formulating products that contain one or more species from both genera to improve the colonisation of probiotics in both the small and large intestines.

The best-documented health benefits associated with probiotic use are:

decreased incidence or duration of diarrhoea caused by antibiotics or viruses;2,3,4

improved symptoms of irritable bowel syndrome (IBS) and other inflammatory bowel disorders such as ulcerative colitis (UC) and Crohn's disease,15,16 but the research is conflicting and the extent of these effects require additional confirmation.

It should also be noted that not every well-conducted probiotics study has shown benefit. Examples of equivocacy include trials related to antibiotic-associated diarrhoea, prevention of surgical infections, improvement of symptoms of IBS, remission in Crohn's disease, postantibiotic vulvovaginal candidiasis and improvements in critically ill hospitalised patients. Yet, because other studies have shown a benefit in these health-related parameters using various probiotic species, researchers speculate that failure to show benefit in these specific studies may be due to lack of product activity, improper probiotic-strain choice, inadequate dose, or inadequate treatment timing and/or duration.17

Gastrointestinal healthDiarrhoea
Consistent and good-quality research supports the use of probiotics for antibiotic-associated diarrhoea and acute infectious diarrhoea such as traveler's diarrhoea or viral-related diarrhoea.18 For instance, a recent meta-analysis of 34 studies found that probiotics reduce the risk of antibiotic-associated diarrhoea by 52 per cent and acute diarrhoea risk in children by 57 per cent and 26 per cent in adults. The species of probiotic shown to be effective were L acidophilus, L rhamnosus GG, L bulgaricus and Saccharomyces boularrdii.19

Another meta-analysis found that these strains were more effective than placebo when given to patients to help prevent and treat antibiotic-associated diarrhoea.18 In addition, a combination of L acidophilus and L casei has been shown to reduce the occurrence of antibiotic-associated diarrhoea and length of hospital duration compared to placebo in hospitalised patients.20 Other studies have concluded that probiotics from various lactobacillus and bifidobacterium species could reduce the risk and duration of infectious diarrhoea from various causes (eg, traveler's diarrhoea, viral diarrhoea) in adults.21,22 Studies also indicate that L reuteri and B lactis are effective in reducing the incidence and duration of diarrhoeal illness in children.23

Constipation
Experimental studies indicate that intestinal transit time (ie, the time it takes for faecal matter to move through the intestines) is prolonged when microflora are absent in germ-free animals compared to those with established microflora.24 The benefit of healthy gut microflora on regularity has also been shown in humans taking specific probiotics. For instance, research supports improvements in gut microflora with the use of L acidophilus and B lactis with accompanying improvements in bowel-movement frequency.25,26,27,28 In addition, at least two trials have found two different strains of L casei can help relieve constipation. One study involved children given L casei rhamnosus and the other study used L casei Shirota in adults with both studies showing improvements in stool frequency and consistency.29,30

Inflammatory bowel
This condition refers to disorders of unknown cause that are characterised by recurrent intestinal inflammation. Such disorders include UC, IBS, Crohn's disease and pouchitis.31 Although some promising findings have been reported with the use of probiotics in these inflammatory conditions, additional studies are needed to confirm which probiotic species function most effectively for each condition, as well as a therapeutic dose range.

To date, the strongest findings are in favour of probiotic use in UC and IBS. In addition, a specific probiotic blend (VSL#3) has been shown to improve remission in patients with pouchitis, an inflammatory condition of the small intestine that can occur after gastrointestinal surgery due to various intestinal problems.32

At least nine randomised, controlled studies have reported a significantly higher remission in UC patients taking probiotics compared with controls, while two studies showed a trend for increased efficacy and five trials did not show any significant difference between probiotic and control groups.15 Interestingly, researchers have documented significant changes in microbial profiles in patients with IBS and indicate that the composition may be correlated with certain symptoms reported by patients.33 Currently, trials evaluating the effect of probiotics in IBS are limited; however, overall researchers report a beneficial effect over placebo in the relief of some IBS symptoms.33

For example, one large controlled trial found that B infantis was significantly more effective at reducing abdominal pain and discomfort in women with IBS compared to those taking placebo.34 Another controlled trial found that L plantarum given to women with IBS for four weeks significantly reduced abdominal pain and improved overall IBS symptoms compared to placebo.35 However, one controlled study evaluating the use of L casei GG did not find any significant improvement in pain, urgency or bloating in women with IBS, but did note a trend in the reduction of the frequency of diarrhoea.36

Benefits of multiple strains
Although isolating and studying single strains of bacteria were the way to go, today scientists have an interest in the benefits of combinations of probiotic strains. As a result, a variety of clinical studies have evaluated the efficacy and safety of multiple-strain probiotic formulations in various populations.10,37,38,39,40,41 In fact, some researchers have suggested that a mixture of probiotics may have a greater effect on the intestine than the individual strains.42,43 Not only have research studies found that multiple strains of probiotics can enhance adhesion of other probiotics to the intestinal wall and increase the richness and diversity of the bacterial microbiota in the gut, but these combinations offer functional benefits as well.43,44,45

For example, experimental research has found that a combination of B bifidum, B infantis, L acidophilus, L casei, L salivarius and B lactis resulted in a wider antimicrobial spectrum, superior induction of anti-inflammatory compounds such as interleukin-10, and silencing of pro-inflammatory cytokines as compared to the individual strains.46 Evidence in humans also suggests that a combination of strains47 rather than a single organism48 may alleviate symptoms of specific gastrointestinal concerns such as those accompanying inflammation of the GI tract. The multi-strain formula contained four strains of lactobacilli, three strains of bifidobacteria and one strain of Streptococcus salivarius ssp thermophilus, as opposed to just a single strain of lactobacilli.

Other studies have found similar results. For example, combinations of lactobacilli, bifidobacteria and S salivarius have been shown to reduce the relapse of recurrent GI symptoms.49 In addition, a probiotic mixture containing L rhamnosus GG, B breve and Propionibacterium freudenreichii ssp Shermanii was effective in alleviating IBS symptoms such as abdominal pain, distension and flatulence.50 Other researchers have found that a similar combination of probiotics (substituting B breve for B lactis) can stabilise microflora levels in IBS patients and reduce abdominal pain and distention.51

Furthermore, a combination of L plantarum and B breve or L plantarum and L acidophilus has been shown to be effective for reducing abdominal pain and symptom severity score in IBS patients.52 A blend of L paracasei and the prebiotic arabinogalactan was also effective in IBS-predominant diarrhoea with significant reductions in bowel movements, pain and IBS scores being reported.53

Other research has evaluated a combination of lactobacilli and bifidobacteria given to individuals put on conventional antibiotic therapy. After eight weeks, the group taking the probiotic/antibiotic combination was able to better tolerate the conventional treatment.54 Furthermore, a multi-strain formula containing B lactis, L paracasei and several other bifidobacteria and lactobacilli species reduced antibiotic-induced microflora imbalance and maintained bifidobacterium levels.55

Jacques Goulet, professor at University de Laval, commented, "From a scientific point of view we are noticing that a single strain won't do the best job in improving health. Scientists are suggesting that probiotic supplements be a mixture of four, five and even eight strains to get the most benefit."56

Not all probiotics are created equal
Products contain different genera (eg, Lactobacillus), species (eg, rhamnosus) and strains (eg, GG or GR-1), and not all microbes sold as probiotics have been tested for health effects, nor should all products be expected to work the same. Therefore, manufacturers that provide clinically validated species of probiotics should specify the intended function and benefit of the strains used on the label and other marketing material, and should recommend the therapeutic dosage of probiotics based on clinical research. In general, research studies have consistently shown that various strains of L acidophilus, L rhamnosus, L casei, B bifidum, B longum, B lactis, L paracasei and others can survive stomach acid and have beneficial effects on gastrointestinal and/or immune health. However, it should be noted that some microencapsulation or coating technologies (eg, enteric coating) have been developed that improve probiotic survival through the acid environment of the stomach, and may influence effectiveness.17

Dosage
Required doses vary for different strains and the specific health effect under investigation. For example, the most common dosage used in clinicals for antibiotic-associated diarrhoea was 3 billion CFUs daily of L acidophilus or L rhamnosus, but studies using 10 billion CFUs or more daily showed greater effectiveness.18 Clinicals showing a benefit for constipation used at least one billion CFUs daily of B lactis or a combination of L acidophilus and B lactis in doses ranging from 1-200 billion CFUs daily.25,26,27,28 Other strains shown to improve constipation were L casei rhamnosus (two billion CFUs/d)29 or L casei Shirota (6.5 billion CFUs/d).30

Get your formula right
Remember, probiotics offer no benefits if they do not contain the right probiotic strains, right potency, right formula and if they are not acid- and bile-resistant. For the real deal on selection criteria for probiotics — from gene technology to GMPs — written by SK Dash, PhD, president and director of research at UAS Laboratories, click here.

While some research has reported some improvement in IBS with moderate doses of 100 million to 20 billion CFUs/day B infantis and L plantarum, respectively,34,35 much higher doses (ie, 900 billion CFUs/day)57 may be required in individuals that are critically ill or that have more serious conditions such as pouchitis or UC (1,800-3,600 billion CFUs/d).32,58,59

Most importantly, probiotics need to be consumed at least a few times a week, preferably daily, on a regular basis to maintain their effect on the intestinal microecology. For instance, levels of bifidobacteria in the colon have been reported to decline with age 55 and lactobacilli concentrations may be negatively influenced by stress.60,61 Preliminary research has found that supplementing the diet with several probiotic species can restore levels of important immune system markers comparable to levels in younger controls,62 and that probiotics may counteract stress-induced changes in intestinal barrier function.61

$937 million us condition-specific digestive health supplements market in 2007

How does gut health relate to immune health?
The gastrointestinal tract is the body's primary immune organ with 70-80 per cent of the body's immune cells being localised in the gastrointestinal tract, its glands, mucosa and mucosa-associated lymphoid system.1,2 A substantial amount of research and significant scientific agreement in the literature supports the ability of various probiotic species to help support immunity.3,4,5

Researchers have documented interactions between probiotics and the gut-associated lymphatic or immune tissue. For instance, experiments that compared specific germ-free and normal mice and rats have shown the strong influence of the presence of intestinal flora on the maturation and development of local and systemic immunity and on the regulation of immune functions.3 In humans, probiotics administered to critically ill patients have shown significant improvements in systemic immunoglobulin (ie, IgA and IgG) concentrations with a corresponding reduction in intestinal permeability.6

L acidophilus and B bifidum appear to enhance nonspecific immune activity.5 They seem to do this by stimulating lymphocyte and macrophage activity and modulating cytokine production by mononuclear cells. They also appear to enhance synthesis of antibodies in response to microbial pathogens, particularly secretory IgA.7,8 Various other species, including L plantarum, L rhamnosus, L casei, L bulgaricus, B lactis, and L paracasei, have demonstrated a variety of immuno-regulatory effects that could help bolster an individual's immune protection.9,10,11 For instance, clinical research suggests that L rhamnosus and L casei can enhance natural killer-cell activity.12,13

In 2007, the U.S. prebiotics market was worth $68.9 million. Growth is expected to be strong throughout the forecast period, leading to revenues of $198.3 million in 2014
In 2007, the leading prebiotics products:

fructans (inulin and FOS), 43.4% of the volumes

MOS accounted for 23.4%

Other prebiotcs, 33.2%

Source: Frost & Sullivan, 2007

How probiotics work
A variety of functions have been attributed to probiotic bacteria, including inhibition of the growth of pathogenic bacteria in the gut, creation of substances that help fuel and reinforce the barrier defense of the gastrointestinal (GI) tract, assisting in the generation and absorption of certain vitamins, influencing the maturation and maintenance of the immune system, production of anti-inflammatory compounds, and antioxidant and cellular protection.1,2

When probiotics latch on to and temporarily colonise the intestinal mucosa, they help prevent attachment of pathogenic bacteria. This ability of colonic microflora to help resist colonisation of pathogenic bacteria is now well established as an essential function of probiotics. Given the complexity of the intestinal ecosystem, the exact mechanisms have yet to be fully elucidated; however, several mechanisms appear to be involved and to act separately, sequentially, or together, and include:

exhaustion or competition for the same substrate or nutrient;

competition for mucin adhesion receptor sites;

production of a physiologically restrictive environment, for instance with respect to pH, redox potential, hydrogen sulfide production or production of metabolites toxic to other bacteria;

in vivo production of antibiotic substances such as bacteriocins;1,3,4,5

Select suppliers: Probiotics, prebiotics and more round out a healthy categoryADM/Matsutani
Fibersol-2 digestion-resistant maltodextrin allows an increased fibre content with no change to taste or texture.www.fibersol2.com

Danisco
Probiotics supplier has exclusive marketing agreement for the probiotic-straw concept for use with Howaru probiotics. Also offers polydextrose as a dietary fibre.www.danisco.com

Decas Botanical Synergies
CystiCran is a concentrated cranberry extract, with a guaranteed minimum content of 30 per cent (PACs). Launched in a partnership between Lallemand Health Ingredients and Decas.www.lallemandhi.com

Lonza
FiberAid soluble prebiotic fibre with good digestive tolerance and technological properties, is water soluble, stable against a wide pH and temperature range and forms low-viscosity solutions.www.lonza.com

National Enzyme Company
Enzyme ingredients range from Dr Howell's original Genuine NZime #1 to the most advanced BioCore Optimum blend.www.nationalenzyme.com

Natraceutical Group
Viscofiber is a concentrated, soluble dietary fibre from oat grain.www.viscofiber.com

Nebraska Cultures
Custom-manufactured probiotics founded on the DDS-1 strain of L acidophilus. Full line available either individually or in combination, and with or without enzymes, colostrum or phytonutrients.www.nebraskacultures.com

Probi
Probiotic R&D with stomach and gastrointestinal tracts, immune defense, metabolic disorders as well as stress and recovery.www.probi.com

Roquette
Nutriose is a range of soluble fibres with 85 per cent fibre content (dry substance), which studies show matches up well with probiotics Streptococcus thermophilus and Lactobacillus bulgaricus.www.nutriose.com